Researchers at the Houston Methodist Research Institute discovered that the blood pressure medication Candesartan cilexetil can disrupt the cell membranes of antibiotic-resistant MRSA bacteria, offering a potential new treatment for severe bacterial infections.
A blood pressure drug has the potential to combat one of the most common, difficult-to-treat bacterial infections, according to a new study. A team of researchers, led by scientists at the Houston Methodist Research Institute in Texas, has shown that the drugIn lab and animal studies, the medicine disrupted the bacteria's cell membrane, interfering with cellular function and ultimately killing the bacteria.
"I think that CC is one of the most exciting agents that we have found," Eleftherios Mylokanis, the study's senior author, told ScienceAlert. Antibiotic-resistant microbes such as MRSA are a rising public health threat. Mylokanis is an infectious disease specialist at Houston Methodist Academic Institute and says MRSA is one of the most common resistant pathogens he sees.
MRSA can cause skin, lung, or even bloodstream infections and results in more than 70,000 severe infections and 9,000 deaths in the US every year, according, attempts to develop new drugs aren't keeping pace with the problem. That's in part because antibiotics aren't very profitable and companies don't have a strong financial incentive to develop them, Mylokanis said.
"The better the antibiotic, we try not to use it, because we worry it will develop resistance. ", they used worms infected with MRSA to screen more than 80,000 compounds. Only a handful of the drugs helped the worms successfully fight off the infection, and Candesartan cilexetil was one of them. To further probe Candesartan cilexetil's potential, the team analyzed its interaction with MRSA with simulations and advanced imaging techniques.
They also analyzed the genetic material, small molecules and lipids involved and tested how well the drug worked on MRSA in the lab when combined with different antibiotics.
"We started building one by one, block by block," Houston Methodist microbiologist Nagendran Tharmalingam, first author of the study, told ScienceAlert. The membrane is a critical part of the cell, providing structure and acting as a gatekeeper to the cell's insides. By latching onto, penetrating, and disrupting the MRSA cell membrane, the drug weakened and killed the bacteria. Imaging studies showed the drug punctured holes in the bacteria's membrane, through which the cell's innards leaked.
Simulations showed how CC penetrates the MRSA membrane, with imaging revealing membrane deformations and extensive damage in CC-treated cells compared to untreated bacteria . (Tharmalingam et al. ,The team also found that Candesartan cilexetil can help fight off persistent MRSA bacteria that can hide dormant in the body and later reemerge. What's more, combining Candesartan cilexetil with existing antibiotics, such as gentamicin, created a stronger response at lower doses than each drug alone.
In mouse models, Candesartan cilexetil significantly reduced the bacterial burden, providing more evidence that the drug could hold promise for fighting MRSA in humans. The team is developing similar drugs, chemically tweaking Candesartan cilexetil to make new compounds that are more effective and potentially have fewer side effects, Tharmalingam said. They are hoping to work with a pharmaceutical or biotech company to further test Candesartan cilexetil and similar compounds in human trials, with positive responses so far.
MRSA Antibiotic Resistance Candesartan Cilexetil Medical Research Bacterial Infections
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